High density lipoprotein (HDL) levels inversely correlate with atherosclerosis. HDL appear to be involved in the removal of cholesterol from the body by reverse cholesterol transport. The exact biological mechanisms involved in this process are not well understood, at least in part, due to the complexity of HDL. The overall hypothesis of this project is that HDL are a collection of discrete subspecies, each of which may have a unique biological function. This proposal has three specific aims: (1) Two newly defined HDL subfractions, heparin-binding HDL and HDL derived from human atherosclerotic aortic plaque, will be isolated and characterized. These lipoproteins will be isolated by selected affinity immunosorption, a technique which is minimally perturbing to HDL structure. (2) We have proposed a model suggesting that the interconversion between pre-beta HDL and alpha HDL subfractions is connected to the movement of cholesterol through HDL. Specific facets of this model will be investigated by in vitro incubations and particle characterization. (3) Determine if the major sites of HDL degradation in the body, the liver and kidney, selectively degrade unique HDL subspecies. Such information is essential to understanding the biochemical basis by which HDL species function. Information so gathered may be exploited to enhance the apparent protective effect of HDL against atherosclerosis.